Posts tagged neurodegenerative diseases
Articles and news from the latest research reports.
Biomarkers May Aid Differential Diagnosis of Dementias, Parkinsonism
Measurements of five protein biomarkers in the cerebrospinal fluid helped to differentiate Alzheimer’s disease from Parkinson’s disease with dementia and from dementia with Lewy bodies in a cross-sectional study of individuals at Swedish neurology and memory disorder clinics.
The diagnostic accuracy of this panel of tests in distinguishing Alzheimer’s disease from dementia with Lewy bodies “is at least in the same order of magnitude as that obtained with dopamine transporter imaging, and with a lower cost,” Dr. Sara Hall of the department of clinical sciences, Lund (Sweden) University, Malmö, and her associates wrote in a study published Aug. 27 in Archives of Neurology.
In addition, one of the five biomarkers in this panel appears to differentiate Parkinson’s disease from atypical parkinsonism such as that seen in progressive supranuclear palsy, multiple system atrophy, or corticobasal degeneration, the researchers noted.
Their results confirmed those of previous studies postulating that CSF total tau (T-tau) and phophorylated tau (P-tau) levels are higher in Alzheimer’s than in the other two dementias, whereas amyloid-beta (Abeta) 1-42 levels are lower in Alzheimer’s than in the other two dementias.
(Source: acep.org)
Researchers at Carnegie-Mellon University (CMU) are working with a Canadian startup called Autonomous ID to develop biometric shoes that can identify who you are by the way you walk.
The BioSoles can record the pressure points of someone’s feet, track their gait and use a microcomputer to compare that to a master file already made for that person. If the patterns match, the BioSoles stay silent. If they don’t, they transmit a wireless alarm message.
Since the devices are designed to detect changes in gait, some think they could end up being used to help spot early signs of Alzheimer’s disease.
Goldilocks was on to something when she preferred everything “just right.” Harvard Medical School researchers have found that when it comes to the length of mitochondria, the power-producing organelles, applying the fairy tale’s mantra is crucial to the health of a cell. More specifically, abnormalities in mitochondrial length promote the development of neurodegenerative diseases such as Alzheimer’s.
"There had been a fair amount of interest in mitochondria in Alzheimer’s and tau-related diseases, but causality was unknown," said Brian DuBoff, first author of the study and a post-doctoral research fellow at Massachusetts General Hospital.
"Ultimately, a deeper understanding of the relationship between mitochondrial function and Alzheimer’s may guide us to develop more targeted therapies in the future," said Mel Feany, HMS professor of pathology at Brigham and Women’s Hospital and senior author of the paper.
The findings were published online in the August 23 issue of Neuron.
Low oxygen boosts stem cell survival in muscular dystrophy therapy
Controlling the amount of oxygen that stem cells are exposed to can significantly increase the effectiveness of a procedure meant to combat an often fatal form of muscular dystrophy, according to Purdue University research.
A genetic mutation in patients with Duchenne muscular dystrophy causes the constant breakdown of muscles and gradual depletion of stem cells that are responsible for repairing the damage and progressive muscle wasting. A healthy stem cell tends to duplicate in a regular pattern that creates one copy of itself that continues to function as a stem cell, and a differentiated cell, which performs a specific function. In a healthy person, a torn or damaged muscle would be repaired through this process.
Stem cell therapy - implanting healthy stem cells to combat tissue wasting - has shown promise against muscular dystrophy and other neurodegenerative diseases, but few of the implanted stem cells survive the procedure. Shihuan Kuang, a Purdue assistant professor of animal sciences, and Weiyi Liu, a postdoctoral research associate, showed that survival of implanted muscle stem cells could be increased by as much as fivefold in a mouse model if the cells are cultured under oxygen levels similar to those found in human muscles.
"Stem cells survive in a microenvironment in the body that has a low oxygen level," Kuang said. "But when we culture cells, there is a lot of oxygen around the petri dish. We wanted to see if less oxygen could mimic that microenvironment. When we did that, we saw that more stem cells survived the transplant."
Liu thinks that’s because the stem cells grown in higher oxygen levels acclimate to their surroundings. When they’re injected into muscles with lower oxygen levels, they essentially suffocate.
"By contrast, in our study the cells become used to the host environment when they are conditioned under low oxygen levels prior to transplantation," Liu said.
In the mouse model, Kuang and Liu saw more stem cells survive the transplants, and those stem cells retained their ability to duplicate themselves.
"When we lower the oxygen level, we can also maintain the self-renewal process," Kuang said. "If these stem cells self-renew, they should never be used up and should continue to repair damaged muscle."
The findings, reported in the journal Development, shows promise for increasing the effectiveness of stem cell therapy for patients with Duchenne muscular dystrophy, which affects about one in 3,500 boys starting at about 3-5 years old. The disease, which confines almost all patients to wheelchairs by their 20s, is often fatal as muscles that control the abilities to breathe and eat deteriorate.
Source: Purdue University
Scientists Discover Previously Unknown Cleansing System in Brain
A previously unrecognized system that drains waste from the brain at a rapid clip has been discovered by neuroscientists at the University of Rochester Medical Center. The findings were published online August 15 in Science Translational Medicine.
The highly organized system acts like a series of pipes that piggyback on the brain’s blood vessels, sort of a shadow plumbing system that seems to serve much the same function in the brain as the lymph system does in the rest of the body – to drain away waste products.
“Waste clearance is of central importance to every organ, and there have been long-standing questions about how the brain gets rid of its waste,” said Maiken Nedergaard, M.D., D.M.Sc., senior author of the paper and co-director of the University’s Center for Translational Neuromedicine. This work shows that the brain is cleansing itself in a more organized way and on a much larger scale than has been realized previously.
Fixing the way we fix the brain
Of all the health challenges humans face, few are as insidious as those that involve the death or dysfunction of cells in our brains. These illnesses, a category known as neurodegenerative disease, take from us the very things that make us who we are — our thoughts and our memories, our ability to recognize loved ones, control of our bodies, even our cognitive identity.
For most, diseases such as Alzheimer’s or Parkinson’s attack slowly, leading us down a slope of gradually deteriorating mental or physical function that current scientific methods are able to diagnose only after debilitating symptoms have set in. Even if discovered early, there is no way to prevent their onset, no way to reverse the damage, and no cures.
Driven by the desperate need for better understanding and treatments, a coalition of academic researchers, pharmaceutical companies, and state government is now coming together to confront this challenge in a novel way.
What links Alzheimer’s disease, the bridges of Königsberg and Twitter?
A mathematical puzzle originating in 18th century Prussia has led to insights in fields as diverse as banking, social networking, epidemiology – and now Alzheimer’s disease
The progression of Alzheimer’s is accompanied by a buildup in the brain of amyloid plaque and the breakdown of communication between nerve cells. Recent research suggests that graph theory can provide fascinating insights into the faulty wiring behind the progressive memory loss of Alzheimer’s. But what exactly is graph theory?
To discover the origins of the theory we have to go back to the 18th century and the ancient Prussian city of Königsberg, now Kaliningrad – that tiny city state wedged between Poland and Lithuania. It was here that Leonard Euler solved the long-standing Bridges of Königsberg Problem, which has had a profound effect on the development of network theory.
Stress May Cause Women’s Brains to Age Earlier
By Makini Brice | July 26, 2012
Scientists were surprised, expecting the areas of the brain to age more slowly, or even delayed, than those of men.
Photo: Microsoft
Even though the gap is closing now in many high-income countries, on average, women tend to live longer lives than men do. Despite – or perhaps because of – women’s physical longevity, women tend to battle cognitive decline in much greater numbers than men do. In fact, women are more likely to suffer from various types of dementia, including the much-maligned Alzheimer’s disease. Now researchers think that they have an answer to the cause of this double-edged sword: stress. Specifically, stress ages women’s brains more quickly than it does men.
Scientists, and every-day observers, have noted that some body parts age at different rates than others do. As people become older, some genes become more active while others become less so. These changes in activity can be monitored through a “transcriptome,” which collects data on all the RNA – the transcripts that carry DNA’s instructions to cells. A multinational team from Australia, China, Germany, and the United States set out to analyze the transcriptomes for 55 different men and women of various ages.
The researchers were fascinated by what they found. According to the abstract of their article published in Aging Cell, “In the superior frontal gyrus (SFG), a part of the prefrontal cortex, we observed manifest differences between the two sexes in the timing of age-related changes, i.e.sexual heterochrony. Intriguingly, age-related expression changes predominantly occurred earlier, or at a faster pace, in females compared to males. These changes included decreased energy production and neural function, and up-regulation of the immune response, all major features of brain aging.”
In other words, researchers found that the brains of women aged more quickly than those of men, especially in the prefrontal cortex. Scientists were surprised, expecting the areas of the brain to age more slowly, or even delayed, than those of men.
In the superior frontal gyrus, researchers found 667 genes that were expressed differently by gender during the aging process. Within that number, 98 percent were associated with faster aging in women.
Scientists were not convinced that the reason lay in biological differences. In fact, since only half of women displayed accelerated aging, they were convinced that the difference was environmental. Researchers theorize that stress is the difference-maker, and that it affects women’s brains more severely than it does men. While a researcher unaffiliated with the study said that the difference could also be caused by inflammation,
Mehmet Somel and his team have conducted similar research on monkeys that confirms their stress theory.
Source: Medical Daily
A protein essential for metabolism and recently associated with neurodegenerative diseases also occurs in several brain-specific forms. This discovery emerged in the course of a research project funded by the Austrian Science Fund FWF, the findings of which have now been published in the journal Human Molecular Genetics. The scientists working on the project discovered a large new region in the genetic code of the protein PGC-1alpha. Previously unknown variations of the protein, which can be found specifically in the brain, are produced from this region. This discovery may provide tissue-specific starting points for the development of new treatments for neurodegenerative diseases like Huntington’s, Parkinson’s and Alzheimer’s.
PGC-1alpha is a real jack-of-all-trades. As a central regulator of metabolic genes that coordinate energy metabolism, the protein, which functions as a “transcriptional coactivator”, influences major body functions. The extent to which the protein also influences medical conditions like obesity, diabetes and metabolic syndrome is unclear, and was under further investigation as part of a research project funded by the Austrian Science Fund FWF. In the course of their research, however, the scientists stumbled on unexpected findings with a particular relevance for neurodegenerative diseases.
Major Difference
A research team headed by Prof. Wolfgang Patsch from the Departments of Pharmacology and Toxicology, and Laboratory Medicine at the Paracelsus Medical University established that the gene which codes for PGC-1alpha (PPARGC1A) is six times larger than hitherto assumed. A new promoter was actually found at some distance (ca. 580 kb) from the previously known gene. A promoter is a DNA segment usually occurring upstream from a gene that can ultimately control how that gene is expressed as a protein. The transmission of genetic information from DNA to RNA molecules, i.e. transcription, is an important intermediate step in this process.
Transcripts, which are produced from the newly discovered promoter, were now examined in detail as part of the research project. “These transcripts differ in important regions from those encoded by the previously characterized - reference - PPARGC1A locus. Based on these differences, we were able to show that these previously unknown transcripts are produced specifically in human brain cells and are at least as common there as the reference transcripts,” explains Dr. Selma M. Soyal, first author of the article currently published in Human Molecular Genetics. Further analyzes showed that the differences in the transcripts lead to the formation of proteins which differ from the protein that acts as a reference, in particular at the N-terminus. Other differences were found within the PGC-1alpha amino acid chain.
When the different PGC-1alpha proteins were localized in human cells (SH-SY5Y), another surprise awaited the scientists: whereas the reference protein was located mainly in the cell nucleus, one of the newly discovered variants was mainly found in the surrounding cytoplasm; another was found both in the nucleus and in the cytoplasm. According to Prof. Patsch: “It is likely that the differences we found in the transcripts influence mechanisms in the finished proteins which control their localization in the cell.”
A Protein With Impact
The detailed functional characterization of the brain-specific proteins could prove significant, as PGC-1alpha is associated with various neurodegenerative diseases such as Huntington’s disease, Parkinson’s and Alzheimer’s - a link that was also confirmed by the project. Using complex statistical analyses, sequence differences in the new promoter were examined in 1.706 Huntington patients as part of a collaboration with the European Huntington’s Disease Network. A clear correlation emerged here between different sequence patterns and the age of onset of the disease in the patients. In addition, the scientists were also able to show that the newly discovered promoter is active in nerve tissue. This indicates that it may actually play an important role in the only partly known links between PGC-1alpha and the neurodegenerative diseases in question.
Overall, the findings of this project, which is funded by the Austrian Science Fund FWF, indicate complex functions of PGC-1alpha in humans. If the scientists succeed in reaching a better understanding of this complexity, PGC-1alpha could provide new possibilities for future therapeutic intervention in key neurodegenerative diseases.
New Compounds Inhibit Prion Infection
ScienceDaily (July 23, 2012) — A team of University of Alberta researchers has identified a new class of compounds that inhibit the spread of prions, misfolded proteins in the brain that trigger lethal neurodegenerative diseases in humans and animals.
U of A chemistry researcher Frederick West and his team have developed compounds that clear prions from infected cells derived from the brain.
"When these designer molecules were put into infected cells in our lab experiments, the numbers of misfolded proteins diminished — and in some cases we couldn’t detect any remaining misfolded prions," said West.
West and his collaborators at the U of A’s Centre for Prions and Protein Folding Diseases say this research is not yet a cure, but does open a doorway for developing treatments.
"We’re not ready to inject these compounds in prion-infected cattle," said David Westaway, director of the prion centre. "These initial compounds weren’t created for that end-run scenario but they have passed initial tests in a most promising manner."
West notes that the most promising experimental compounds at this stage are simply too big to be used therapeutically in humans or animals.
Human exposure to prion-triggered brain disorder is limited to rare cases of Creutzfeldt-Jakob or mad cow disease. The researchers say the human form of mad cow disease shows up in one in a million people in industrialized nations, but investigating the disease is nonetheless well worth the time and expense.
"There is a strong likelihood that prion diseases operate in a similar way to neurodegenerative diseases such as Alzheimer’s, which are distressingly common around the world," said West.
Source: Science Daily